RESUMEN
Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent identification of NGLY1 deficiency, a congenital disorder of deglycosylation (CDDG) caused by loss of function of an enzyme involved in fOS metabolism, has elicited increased interest in fOS processing. The catabolism of fOSs has been linked to the activity of a specific cytosolic mannosidase, MAN2C1, which cleaves α1,2-, α1,3-, and α1,6-mannose residues. In this study, we report the clinical, biochemical, and molecular features of six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1; the individuals are from four different families. These individuals exhibit dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Complementation experiments with isogenic MAN2C1-KO HAP1 cells confirm the pathogenicity of three of the identified MAN2C1 variants. We further demonstrate that MAN2C1 variants lead to accumulation and delay in the processing of fOSs in proband-derived cells. These results emphasize the involvement of MAN2C1 in human neurodevelopmental disease and the importance of fOS catabolism.
Asunto(s)
Quistes del Sistema Nervioso Central/genética , Trastornos Congénitos de Glicosilación/genética , Hamartoma/genética , Discapacidad Intelectual/genética , Oligosacáridos/metabolismo , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/deficiencia , Polimicrogiria/genética , alfa-Manosidasa/genética , Adolescente , Alelos , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Línea Celular Tumoral , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/patología , Vermis Cerebeloso/metabolismo , Vermis Cerebeloso/patología , Niño , Preescolar , Trastornos Congénitos de Glicosilación/metabolismo , Trastornos Congénitos de Glicosilación/patología , Femenino , Feto , Glicosilación , Hamartoma/metabolismo , Hamartoma/patología , Humanos , Hipotálamo/metabolismo , Hipotálamo/patología , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/patología , Leucocitos/metabolismo , Leucocitos/patología , Masculino , Manosa/metabolismo , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/genética , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/metabolismo , Polimicrogiria/metabolismo , Polimicrogiria/patología , Lengua/metabolismo , Lengua/patología , alfa-Manosidasa/deficienciaRESUMEN
Direct determination of RNA structures and interactions in living cells is critical for understanding their functions in normal physiology and disease states. Here, we present PARIS2, a dramatically improved method for RNA duplex determination in vivo with >4000-fold higher efficiency than previous methods. PARIS2 captures ribosome binding sites on mRNAs, reporting translation status on a transcriptome scale. Applying PARIS2 to the U8 snoRNA mutated in the neurological disorder LCC, we discover a network of dynamic RNA structures and interactions which are destabilized by patient mutations. We report the first whole genome structure of enterovirus D68, an RNA virus that causes polio-like symptoms, revealing highly dynamic conformations altered by antiviral drugs and different pathogenic strains. We also discover a replication-associated asymmetry on the (+) and (-) strands of the viral genome. This study establishes a powerful technology for efficient interrogation of the RNA structurome and interactome in human diseases.
Asunto(s)
Enfermedades Transmisibles/genética , Enfermedades Transmisibles/metabolismo , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/metabolismo , Fotoquímica/métodos , ARN/química , ARN/metabolismo , Calcinosis/genética , Calcinosis/metabolismo , Quistes del Sistema Nervioso Central/genética , Quistes del Sistema Nervioso Central/metabolismo , Reactivos de Enlaces Cruzados , Enterovirus Humano D/genética , Furocumarinas , Genoma Viral , Humanos , Leucoencefalopatías/genética , Leucoencefalopatías/metabolismo , Modelos Moleculares , Mutación , Conformación de Ácido Nucleico , Procesos Fotoquímicos , ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Nucleolar Pequeño/química , ARN Nucleolar Pequeño/genética , ARN Nucleolar Pequeño/metabolismo , ARN Viral/química , ARN Viral/genéticaRESUMEN
BACKGROUNDMethodology for estimation of cerebrospinal fluid (CSF) tracer clearance could have wide clinical application in predicting excretion of intrathecal drugs and metabolic solutes from brain metabolism and for diagnostic workup of CSF disturbances.METHODSThe MRI contrast agent gadobutrol (Gadovist) was used as a CSF tracer and injected into the lumbar CSF. Gadobutrol is contained outside blood vessels of the CNS and is eliminated along extravascular pathways, analogous to many CNS metabolites and intrathecal drugs. Tracer enrichment was verified and assessed in CSF by MRI at the level of the cisterna magna in parallel with obtaining blood samples through 48 hours.RESULTSIn a reference patient cohort (n = 29), both enrichment within CSF and blood coincided in time. Blood concentration profiles of gadobutrol through 48 hours varied between patients diagnosed with CSF leakage (n = 4), idiopathic normal pressure hydrocephalus dementia (n = 7), pineal cysts (n = 8), and idiopathic intracranial hypertension (n = 4).CONCLUSIONAssessment of CSF tracer clearance is clinically feasible and may provide a way to predict extravascular clearance of intrathecal drugs and endogenous metabolites from the CNS. The peak concentration in blood (at about 10 hours) was preceded by far peak tracer enhancement at MRI in extracranial lymphatic structures (at about 24 hours), as shown in previous studies, indicating a major role of the spinal canal in CSF clearance capacity.FUNDINGThe work was supported by the Department of Neurosurgery, Oslo University Hospital; the Norwegian Institute for Air Research; and the University of Oslo.
Asunto(s)
Quistes del Sistema Nervioso Central/metabolismo , Pérdida de Líquido Cefalorraquídeo/metabolismo , Medios de Contraste/farmacocinética , Sistema Glinfático/metabolismo , Hidrocéfalo Normotenso/metabolismo , Compuestos Organometálicos/farmacocinética , Seudotumor Cerebral/metabolismo , Adulto , Anciano , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Pérdida de Líquido Cefalorraquídeo/diagnóstico por imagen , Femenino , Humanos , Hidrocéfalo Normotenso/diagnóstico por imagen , Inyecciones Espinales , Imagen por Resonancia Magnética , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Glándula Pineal/diagnóstico por imagen , Seudotumor Cerebral/diagnóstico por imagenRESUMEN
Background: Adrenocorticotropic Hormone (ACTH)-dependent Cushing's Syndrome (CS) is most often caused by a pituitary adenoma. Although rarely, it can also result from pituitary corticotroph cell hyperplasia (CH). Reports on concomitant pituitary lesions including ACTH-producing adenomas and Rathke's cleft cysts (RCCs) have been published. Positron emission tomography (PET), using 11C-labelled-methionine (MET) as a tracer and co-registered with magnetic resonance imaging (MRI) has been shown to be useful in the diagnosis of pituitary collision lesions, however, its role is still under investigation. In this work we present the case of a patient in whom CS was caused by non-adenomatous CH within the wall of an RCC. Case Summary: In 2015 a patient with signs and symptoms of CS was referred to our Department. Biochemical studies repeatedly showed elevated midnight serum cortisol and ACTH levels. Magnetic resonance imaging of the sellar region revealed an RCC and MET-PET/MR showed heterogeneous labelled-methionine metabolism in the vicinity of the cyst's wall. Transsphenoidal surgery resulted in rapid, complete and lasting relief of symptoms. Histopathological examination demonstrated an RCC and CH. Conclusions: Concomitance of pituitary focal lesions is a rare phenomenon. Methionine-labelled PET/MR may be useful in the diagnosis of collision sellar lesions, including CH. Corticotroph cell hyperplasia can present as mild and fluctuating hypercortisolaemia.
Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Radioisótopos de Carbono/análisis , Quistes del Sistema Nervioso Central/diagnóstico , Síndrome de Cushing/diagnóstico , Hiperplasia/diagnóstico , Enfermedades de la Hipófisis/diagnóstico , Tomografía de Emisión de Positrones/métodos , Adulto , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/metabolismo , Síndrome de Cushing/complicaciones , Síndrome de Cushing/diagnóstico por imagen , Síndrome de Cushing/metabolismo , Femenino , Humanos , Hiperplasia/complicaciones , Hiperplasia/diagnóstico por imagen , Metionina/metabolismo , Enfermedades de la Hipófisis/complicaciones , Enfermedades de la Hipófisis/diagnóstico por imagen , Enfermedades de la Hipófisis/metabolismoRESUMEN
A 69-year-old woman presented with cognitive impairment related to attentive, executive, and mnemonic functions; progressive worsening of walking, speaking, writing, and reading ability; and double sphincter incontinence. Leukoencephalopathy, cystic lesions, and calcifications, suspected for Labrune syndrome, were observed at MRI and CT brain images. Generalized wave abnormalities were also visible at electroencephalogram. Functional brain imaging performed with F-FDG PET/CT demonstrated a decreased glucose metabolism in impaired brain regions, in accordance with MRI findings. Genetic testing confirmed a mutation of SNORD118.
Asunto(s)
Calcinosis/diagnóstico por imagen , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Leucoencefalopatías/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Calcinosis/genética , Calcinosis/metabolismo , Quistes del Sistema Nervioso Central/genética , Quistes del Sistema Nervioso Central/metabolismo , Glucosa/metabolismo , Humanos , Leucoencefalopatías/genética , Leucoencefalopatías/metabolismo , Imagen por Resonancia Magnética , Masculino , Mutación , ARN Nucleolar Pequeño/genéticaRESUMEN
The transcription factor ISL1 is expressed in pituitary gland stem cells and the thyrotrope and gonadotrope lineages. Pituitary-specific Isl1 deletion causes hypopituitarism with increased stem cell apoptosis, reduced differentiation of thyrotropes and gonadotropes, and reduced body size. Conditional Isl1 deletion causes development of multiple Rathke's cleft-like cysts, with 100% penetrance. Foxa1 and Foxj1 are abnormally expressed in the pituitary gland and associated with a ciliogenic gene-expression program in the cysts. We confirmed expression of FOXA1, FOXJ1, and stem cell markers in human Rathke's cleft cyst tissue, but not craniopharyngiomas, which suggests these transcription factors are useful, pathological markers for diagnosis of Rathke's cleft cysts. These studies support a model whereby expression of ISL1 in pituitary progenitors drives differentiation into thyrotropes and gonadotropes and without it, activation of FOXA1 and FOXJ1 permits development of an oral epithelial cell fate with mucinous cysts. This pituitary-specific Isl1 mouse knockout sheds light on the etiology of Rathke's cleft cysts and the role of ISL1 in normal pituitary development.
Asunto(s)
Quistes del Sistema Nervioso Central/metabolismo , Eliminación de Gen , Proteínas con Homeodominio LIM/deficiencia , Proteínas de Neoplasias/deficiencia , Hipófisis/metabolismo , Células Madre/metabolismo , Factores de Transcripción/deficiencia , Animales , Quistes del Sistema Nervioso Central/genética , Quistes del Sistema Nervioso Central/patología , Proteínas con Homeodominio LIM/metabolismo , Ratones , Ratones Noqueados , Proteínas de Neoplasias/metabolismo , Hipófisis/patología , Células Madre/patología , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Intramedullary ependymal cysts of the spinal cord are rare, benign, fluid-filled cysts usually situated along the ventral surface of the spinal cord. Only 32 cases have been reported since they were first described. Thus, owing to the rarity at which these cysts are encountered, their management and pathogenesis remain controversial. Whereas some investigators have advocated for cystosubarachnoid shunt placement for symptomatic ependymal cysts, others have argued for complete cyst resection or simple fenestration. Here we report the case of a 56-year-old female with a T11-T12 ependymal cyst that was successfully managed with cyst fenestration. We further investigated a potential pathological mechanism of cyst formation by performing immunohistochemistry to detect aquaporin expression in the cyst lining. CASE DESCRIPTION: A 56-year-old female was found to harbor an enlarging cystic lesion of the conus that was discovered on workup of progressive paraparesis and urinary incontinence. She had lower extremity weakness and progressive myelopathy. Thoracic laminectomy with cyst fenestration arrested her neurologic deterioration. Pathological analysis revealed an intramedullary ependymal cyst. Immunohistochemistry was subsequently performed for expression of aquaporin-1 and aquaporin-4. There was dense staining of the underlying neuropil with concurrent membranous staining pattern of the cyst lining. CONCLUSIONS: Intramedullary ependymal cysts are rare, cystic lesions of the spinal cord. Early cyst fenestration decompresses the cyst and prevents neurologic deterioration. Here we report for the first time that aquaporins are expressed in the cyst wall, which is consistent with a passive, osmotic pathogenic mechanism of cyst formation.
Asunto(s)
Acuaporina 1/biosíntesis , Acuaporina 4/biosíntesis , Quistes del Sistema Nervioso Central/metabolismo , Epéndimo/metabolismo , Médula Espinal/metabolismo , Acuaporina 1/genética , Acuaporina 4/genética , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/cirugía , Epéndimo/diagnóstico por imagen , Epéndimo/cirugía , Femenino , Expresión Génica , Humanos , Persona de Mediana Edad , Médula Espinal/diagnóstico por imagen , Médula Espinal/cirugíaRESUMEN
Whether a mixed type of craniopharyngioma (CP) exists and whether papillary craniopharyngioma (pCP) is on a histopathological continuum with Rathke's cleft cyst (RCC) remain controversial. Herein, we examined the expression and localization of ß-catenin, BRAF p.V600E (V600E), and triggering receptor expressed on myeloid cells-1 (TREM-1) in 58 samples including 20 pCPs, 26 adamantinomatous craniopharyngiomas (aCP), and 12 RCCs. Five aCPs were diagnosed with mixed type CPs and the remaining 21 cases were pure aCPs. Four of the 12 RCCs presented with significant squamous epithelium (SE). V600E immunoreactivity was observed in all pCPs in the cytoplasm, but not in the nuclei. aCPs and RCCs, including mixed type CP, did not express V600E. Nuclear ß-catenin translocation was detected exclusively in aCPs. TREM-1 was expressed in pCPs. Additionally, TREM-1 expression was detected in the SE of 5 "mixed type" CPs, while it was absent in pure aCPs. TREM-1 was expressed in 4 RCCs with SE, but not in the remaining 8 RCCs. TREM-1 mRNA levels were compared in cultured pCP and aCP cells. TREM-1 mRNA level was significantly (p < 0.001; up to 4.045 fold) higher in pCPs than in aCPs. Western blotting revealed a significantly (p < 0.001; up to 7.19 fold) lower level of TREM-1 expression in aCP cells compared to that in pCP cells. Our findings further supported that RCC and pCP may represent two ends of a morphological spectrum. A variant showing overlapping histological features of aCP and pCP should not be considered as a mixed type.
Asunto(s)
Quistes del Sistema Nervioso Central/metabolismo , Craneofaringioma/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Adolescente , Adulto , Núcleo Celular/metabolismo , Niño , Citoplasma/metabolismo , Análisis Mutacional de ADN , Exones , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Hipofisarias/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , ARN Mensajero/metabolismo , Adulto Joven , beta Catenina/metabolismoRESUMEN
The epithelial cell adhesion molecule (EpCAM) is a type I glycoprotein located on the surface of epithelial cells. It is strongly expressed in many neoplasms and already used in the diagnosis and distinction of various tumour subtypes. Comparative studies about EpCAM expression in cystic sellar lesions are lacking. Therefore, we analysed its distribution pattern in adamantinomatous (aCP) and papillary (pCP) craniopharyngiomas (CP) and Rathke's Cleft Cysts (RCC) using immunohistochemistry and gene expression profiling. Whereas the protein was not detectable in pCP (n = 10), all aCP (n = 64) showed distinct staining patterns. The vast majority of RCC (n = 10) also appeared positive, but these displayed notably lower labeling scores. Additionally, significantly higher mRNA levels were detectable in aCP (n = 19) when compared to pCP (n = 10) (p = 9.985(-8)). Furthermore, pediatric aCP cases, in general, exhibited stronger EpCAM staining levels compared to adult ones (p = 0.015). However, we were not able to verify this result on mRNA level. In summary, our findings demonstrate that EpCAM can be used as an additional distinction-marker for cystic lesions of the sellar region. Its unknown function in aCP and the presence of an approved monoclonal bispecific trifunctional antibody for cancer therapy are interesting starting points for further studies.
Asunto(s)
Quistes del Sistema Nervioso Central/genética , Craneofaringioma/genética , Molécula de Adhesión Celular Epitelial/genética , Perfilación de la Expresión Génica , Neoplasias Hipofisarias/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Quistes del Sistema Nervioso Central/metabolismo , Niño , Preescolar , Craneofaringioma/metabolismo , Molécula de Adhesión Celular Epitelial/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/metabolismo , Adulto JovenRESUMEN
The analysis of individuals with telomere defects may shed light on the delicate interplay of factors controlling genome stability, premature aging, and cancer. We herein describe two Coats plus patients with telomere and genomic defects; both harbor distinct, novel mutations in STN1, a member of the human CTC1-STN1-TEN1 (CST) complex, thus linking this gene for the first time to a human telomeropathy. We characterized the patients' phenotype, recapitulated it in a zebrafish model and rescued cellular and clinical aspects by the ectopic expression of wild-type STN1 or by thalidomide treatment. Interestingly, a significant lengthy control of the gastrointestinal bleeding in one of our patients was achieved by thalidomide treatment, exemplifying a successful bed-to-bench-and-back approach.
Asunto(s)
Ataxia , Neoplasias Encefálicas , Calcinosis , Quistes del Sistema Nervioso Central , Regulación de la Expresión Génica/efectos de los fármacos , Leucoencefalopatías , Espasticidad Muscular , Mutación , Enfermedades de la Retina , Convulsiones , Proteínas de Unión a Telómeros , Telómero , Talidomida/administración & dosificación , Animales , Ataxia/tratamiento farmacológico , Ataxia/genética , Ataxia/metabolismo , Ataxia/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Calcinosis/tratamiento farmacológico , Calcinosis/genética , Calcinosis/metabolismo , Calcinosis/patología , Quistes del Sistema Nervioso Central/tratamiento farmacológico , Quistes del Sistema Nervioso Central/genética , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Leucoencefalopatías/tratamiento farmacológico , Leucoencefalopatías/genética , Leucoencefalopatías/metabolismo , Leucoencefalopatías/patología , Masculino , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/genética , Espasticidad Muscular/metabolismo , Espasticidad Muscular/patología , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/genética , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patología , Convulsiones/tratamiento farmacológico , Convulsiones/genética , Convulsiones/metabolismo , Convulsiones/patología , Telómero/genética , Telómero/metabolismo , Telómero/patología , Proteínas de Unión a Telómeros/biosíntesis , Proteínas de Unión a Telómeros/genética , Talidomida/efectos adversos , Pez CebraRESUMEN
BACKGROUND: While most pineal cysts (PCs) are asymptomatic, some PCs are accompanied with symptoms of variable severity. We suggested that symptom severity in symptomatic patients with non-hydrocephalic PCs relates to venous compression causing central venous hypertension. This study explored whether possible magnetic resonance imaging (MRI) biomarkers of central venous hypertension could differentiate the severity of symptoms in individuals with non-hydrocephalic PCs. METHODS: The study included all individuals with PCs and MRI available for analysis followed conservatively within the department from 2003 to 2014. Severity of symptoms at follow-up were assessed from a questionnaire. Suggested MRI biomarkers indicative of central venous hypertension were explored, in addition to MRI measures of cyst size, aqueduct stenosis, and tectal compression. RESULTS: The study included 66 patients. As compared to the 27/66 patients (41%) with "None-Moderate" symptoms at follow-up, the 39/66 patients (59%) with "Much-Severe" symptoms presented with significantly altered indices of central venous hypertension (tectum-splenium-cyst ratio and indices of thalamic and periventricular edema). PC grading based on MRI biomarkers of central venous hypertension differentiated the severity of symptoms. CONCLUSION: The results indicate an association between severity of symptoms and MRI biomarkers of central venous hypertension in symptomatic individuals with non-hydrocephalic PCs.
Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Hipertensión/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Pinealoma/diagnóstico por imagen , Adulto , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/metabolismo , Quistes del Sistema Nervioso Central/epidemiología , Quistes del Sistema Nervioso Central/metabolismo , Presión Venosa Central , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Hipertensión/metabolismo , Masculino , Pinealoma/epidemiología , Pinealoma/metabolismoRESUMEN
Antibodies that recognize neo-epitopes in tumor cells are valuable tools in the evaluation of tissue biopsy or resection specimens. The VE1 antibody that recognizes the V600E-mutant BRAF protein is one such example. We have recently shown that the vast majority of papillary craniopharyngiomas-tumors that arise in the sellar or suprasellar regions of the brain-harbor BRAF V600E mutations. The VE1 antibody can be effective in discriminating papillary craniopharyngioma from adamantinomatous craniopharyngioma, which harbors mutations in CTNNB1 and not BRAF. While further characterizing the use of the VE1 antibody in the differential diagnosis of suprasellar lesions, we found that the VE1 antibody stains the epithelial cells lining Rathke's cleft cysts with very strong staining of the cilia of these cells. We used targeted sequencing to show that Rathke's cleft cysts do not harbor the BRAF V600E mutation. Moreover, we found that the VE1 antibody reacts strongly with cilia in various structures-the bronchial airways, the fallopian tubes, the nasopharynx, and the epididymis-as well as with the flagella of sperm. In addition, VE1 reacts strongly with the cilia of the ependymal lining of the brain and with the cilia-containing microlumens of ependymoma tumors. There is significant sequence homology between the synthetic peptide (amino acid 596-606 of BRAF V600E: GLATEKSRWSG) that was used to generate the VE1 antibody and regions of multiple axonemal dynein heavy chain proteins (eg, DNAH2, DNAH7, and DNAH12). These proteins are major components of the axonemes of cilia and flagella where they drive the sliding of microtubules. In ELISA assays, we show that the VE1 antibody recognizes epitopes from these proteins. A familiarity with the cross-reactivity of the VE1 antibody with epitopes of proteins in cilia is of value when evaluating tissues stained with this important clinical antibody.
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Anticuerpos Monoclonales , Dineínas Axonemales/metabolismo , Cilios/metabolismo , Epítopos , Proteínas Proto-Oncogénicas B-raf/inmunología , Biomarcadores de Tumor , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/patología , Reacciones Cruzadas , Humanos , Proteínas Proto-Oncogénicas B-raf/metabolismoRESUMEN
Rathke's cleft cysts are benign sellar and suprasellar lesions arising from epithelial remnants of Rathke's pouch with a peak incidence at 30-50 years of age. The majority are between 10 and 20mm in diameter and contain mucoid or gelatinous material encapsulated in a thin cyst wall of simple or pseudostratified cuboidal or columnar epithelium. Symptomatic cases are rare, but incidental lesions are found in 11% of unselected postmortem cases. The pathogenesis of these lesions is uncertain, but they may occasionally share histopathologic features with (papillary) craniopharyngiomas. The most common presenting symptoms include headaches, visual disturbance, and pituitary hormone abnormalities. MRI reveals well-demarcated homogenous lesions with variable intensity that is highly dependent on cyst contents, which can range from clear, CSF-like fluid to thick, mucoid material. Treatment is almost invariably surgical with the aim of draining the cyst contents and removing the surrounding capsule. The recurrence rate is uncertain due to a lack of studies with long follow-up periods, but risk factors associated with increased likelihood of recurrence include cyst size, presence of squamous metaplasia of the cyst wall, incomplete resection or intraoperative CSF leak, and the need for an abdominal fat graft or sellar packing.
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Quistes del Sistema Nervioso Central/diagnóstico , Hipófisis/patología , Animales , Quistes del Sistema Nervioso Central/epidemiología , Quistes del Sistema Nervioso Central/metabolismo , Diabetes Insípida/diagnóstico , Diabetes Insípida/epidemiología , Diabetes Insípida/metabolismo , Cefalea/diagnóstico , Cefalea/epidemiología , Cefalea/metabolismo , HumanosRESUMEN
BACKGROUND: Rathke's cleft cyst (RCC) with significant squamous and/or stratified epithelium including smooth transition from single cuboidal to squamous epithelium (tRCC) is rare and possibly represents an intermediate form to craniopharyngioma. METHODS: Twelve patients with histologically confirmed tRCC were retrospectively investigated from a series of 167 cases of RCC and 96 cases of craniopharyngiomas. Clinical data were reviewed, and immunohistochemistry findings for cytokeratins and ß-catenin were examined. RESULTS: All lesions were located in the sella turcica with marked extension to suprasellar cistern. Six of the 12 patients had suffered postoperative re-enlargement, and three of these six patients required more than two additional operations and irradiation. CAM5.2 was positive in the glandular epithelium in all tRCCs and focally positive in the squamous epithelium of all these tRCCs. 34ßE12 was positive in the squamous epithelium in all tRCCs and focally positive in the glandular epithelium in all but one tRCC. The findings of cytokeratin expression of tRCCs were very similar to those of craniopharyngioma. ß-Catenin showed nuclear translocation in five cases. All patients with nuclear translocation of ß-catenin suffered postoperative re-enlargement. CONCLUSIONS: tRCC carries an extremely high risk of re-enlargement. Cytokeratin expression resembles that in craniopharyngioma, which might indicate a very close origin of these pathologies. Nuclear translocation of ß-catenin may be related to the aggressive clinical course.
Asunto(s)
Quistes del Sistema Nervioso Central/patología , Craneofaringioma/patología , Neoplasias Hipofisarias/patología , Adolescente , Adulto , Anciano , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/cirugía , Niño , Craneofaringioma/metabolismo , Craneofaringioma/cirugía , Femenino , Humanos , Queratinas/metabolismo , Masculino , Metaplasia/metabolismo , Persona de Mediana Edad , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/cirugía , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven , beta Catenina/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Intracranial epidermal cysts are benign uncommon lesions. Such lesions arise from an inclusion of an ectodermal element during neural tube closure, in which dermal elements become trapped in the suture line, diploe, meninges, or scalp. Reports have extensively demonstrated the typical magnetic resonance (MR) spectra with the presence of large lactate signals with a virtual absence of healthy brain metabolites. METHODS: A 20-year-old male patient with a parietal lobe brain lesion was studied by magnetic resonance imaging and magnetic resonance spectroscopy in a 1.5-T Philips scanner. RESULTS: The lesion presented atypical MR spectra with presence of alanine (1.46 ppm), lactate (1.31 ppm), and amino acids such as valine, isoleucine (0.97 ppm), and glicine (3.52 ppm). No evidence of normal parenchyma tissue metabolites (N-acetylaspartate, creatine, and choline) or succinate and acetate signals was observed. This spectral pattern was unexpected being proposed the differential diagnosis of brain abscess versus epidermoid cyst. Finally, surgical total excision biopsy confirmed the diagnosis of epidermal cyst. CONCLUSIONS: In this report, we describe a case of an epidermal cyst with an unusual metabolic pattern observed by magnetic resonance spectroscopy mimicking a brain abscess.
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Absceso Encefálico/diagnóstico , Absceso Encefálico/metabolismo , Quistes del Sistema Nervioso Central/diagnóstico , Quistes del Sistema Nervioso Central/metabolismo , Quiste Epidérmico/diagnóstico , Quiste Epidérmico/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Adulto , Biomarcadores/análisis , Humanos , MasculinoAsunto(s)
Quistes del Sistema Nervioso Central/clasificación , Quistes del Sistema Nervioso Central/patología , Epéndimo/patología , Enfermedades de la Médula Espinal/clasificación , Enfermedades de la Médula Espinal/patología , Quistes del Sistema Nervioso Central/metabolismo , Epéndimo/metabolismo , Humanos , Inmunohistoquímica , Enfermedades de la Médula Espinal/metabolismoRESUMEN
Rathke's cleft cyst is a non-neoplastic sellar cyst, which is increasingly reported on radiological investigation performed for unrelated intra-cranial pathology. When symptomatic, it is associated with headache, visual symptoms, and pituitary dysfunction. We report a case of an 18 year-old male patient with Rathke's cleft cyst, who presented with failing vision, headache, and hypocortisolism. After defaulting on planned surgery, the patient continued to take a replacement dose of prednisolone for a year. He reported significant improvement in vision and remarkable reduction in cyst size on repeat imaging after a year. Surgery was later performed in view of persisting severe headache. The authors discuss the reduction in cyst size in relation to long-term usage of replacement steroid. They postulate that selected patients with Rathke's cleft cyst with radiological evidence of inflammatory fluid can be given a trial of glucocorticoids and assessed for cyst shrinkage and changes in imaging characteristics.
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Corticoesteroides/administración & dosificación , Quistes del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso/tratamiento farmacológico , Adolescente , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/fisiopatología , Quistes del Sistema Nervioso Central/cirugía , Humanos , Masculino , Neoplasias del Sistema Nervioso/metabolismo , Neoplasias del Sistema Nervioso/fisiopatología , Neoplasias del Sistema Nervioso/cirugía , Hormonas Tiroideas/metabolismo , Carga Tumoral/efectos de los fármacosRESUMEN
OBJECTIVE: Rathke's cleft cyst (RCC) may transform to papillary type craniopharyngioma (CP) after squamous metaplasia: this is referred to as ciliated CP. We encountered a case involving a patient who had late development of adamantinomatous CP following surgery for RCC, the details of which may shed light on the histogenesis of CP in general. PATIENT: A 41-year-old man presented to our institution with visual disturbance, and magnetic resonance imaging (MRI) showed a cystic mass in the suprasellar region. The patient underwent a biopsy via a transsphenoidal approach and was diagnosed as having a RCC. 34 months after the initial surgery, the patient revisited our hospital for a rapidly aggravating visual disturbance and underwent neuroendoscopic biopsy and tumor removal via a bifrontal craniotomy. Histologically, the tumor was shown to be an adamantinomatous CP. No nuclear beta-catenin accumulation was detectable in the previous RCC specimen, but nuclear beta-catenin accumulation was found in the recent CP specimen, restricted to whorl-like structures or surrounding ghost cells. CONCLUSIONS: Our case of adamantinomatous CP that developed long after removal of the RCC, diagnosed by beta-catenin staining, supports the hypothesis that CPs may develop from RCCs directly due to beta-catenin mutations. However, it still does not prove that a histogenetic connection can be shown between the two lesions which are clonally unrelated. Our case is reported as two consecutive lesions; this in itself is a rare situation.
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Quistes del Sistema Nervioso Central/patología , Craneofaringioma/patología , Neoplasias Primarias Secundarias/patología , Neoplasias Hipofisarias/patología , Adulto , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/cirugía , Craneofaringioma/metabolismo , Craneofaringioma/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Primarias Secundarias/metabolismo , Neoplasias Primarias Secundarias/cirugía , Procedimientos Neuroquirúrgicos , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/cirugía , beta Catenina/metabolismoRESUMEN
Interleukin-5 and interleukin-10, as important mediators of vascular permeability, contribute to the development of various pathologic effusions. However, little is known regarding the involvement of these two cytokines in the formation of cysts associated with central nervous system (CNS) tumors. Twenty-eight patients with various cystic CNS tumors were investigated for expression of interleukin-5 and interleukin-10 in cyst fluid and their matched cytokine receptors in tumor tissue. Interleukin-5 and interleukin-10 were detected in cyst fluid, and interleukin-5 concentration was significantly correlated with interleukin-10 concentration (r=0.508, p=0.006). Moreover, both receptors were also detectable in the tumor tissue specimens and high levels of expression were also found in perivascular cells. Therefore, the local production of interleukin-5 and interleukin-10 might be implicated in some types of cyst formation.
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Quistes del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/metabolismo , Interleucina-10/metabolismo , Interleucina-5/metabolismo , Quistes del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/patología , Humanos , Receptores de Interleucina-10/metabolismo , Receptores de Interleucina-5/metabolismoRESUMEN
The pars tuberalis is a distinct subdivision of the pituitary gland but its function remains poorly understood. Suprasellar tumors in this pars tuberalis region are frequently accompanied by hyperprolactinemia. As these tumors do not immunoreact for any of the established pituitary hormones, they are classified as nonsecretory. It has been postulated that these suprasellar tumors induce hyperprolactinemia by compressing the pituitary stalk, resulting in impaired dopamine delivery to the pituitary and, consequently, disinhibition of the lactotropes. An alternative hypothesis proposed is that suprasellar tumors secrete a specific pars tuberalis factor that stimulates prolactin secretion. Hypothesized candidates are the preprotachykinin A derived tachykinins, substance P and/or neurokinin A.